Transarterial Interventions Research Articles

Transarterial intervention therapy combined with systemic therapy for HCC: a review of recent five-year articles

Transarterial intervention therapy combined with systemic therapy for HCC: a review of recent five-year articles

Transarterial Coil Embolization for Type II Endoleak After Endovascular Aneurysm Repair (EVAR).

Background Endovascular aneurysm repair (EVAR) has evolved into treatment of choice for infrarenal abdominal aortic aneurysms (AAA). Type II endoleaks, although frequently benign, can lead to sac enlargement and rupture. Management of these endoleaks by endovascular means can be quite challenging and may require complex techniques and assistance of interventional radiologists, not always available in all vascular units. This is a single-center study of management of type II endoleaks with transarterial coil embolization performed by vascular surgeons and with minimum requirements regarding the necessary equipment. Methods From 2017 to 2022, 13 patients with type II endoleak were treated. Local anaesthesia and transfemoral or transbrachial approach was used. The superficial mesenteric artery (SMA) was catheterized and through the Riolan arch, coiling of the inferior mesenteric artery and/or the sac aneurysm was performed. Results The mean time period between the primary EVAR procedure and the transarterial intervention for the endoleak was 3.9 years. Primary technical success was achieved in 11 (84.6%) patients, whilesecondary technical success was 12 (92.3%). In the mean follow-up period, which was 2.6 years, the endoleak was treated successfully in 11 (84.6%) patients. Conclusions Transarterial coil embolization of type II endoleaks is a minimal low-cost procedure, with small percentage of complications, high technical and treatment success rates. It could be considered as a first-line treatment of unresolvable type II endoleaks, minimizing the need for open repair.

Transarterial interventions in civilian gunshot wound injury: experience from a level-1 trauma center

PurposeTo assess the effectiveness of trans-arterial vascular interventions in treatment of civilian gunshot wounds (GSW).Materials and methodsA retrospective review was performed at a level-1 trauma center to include 46 consecutive adults admitted due to GSW related hemorrhage and treated with endovascular interventions from July 2018 to July 2022. Patient demographics and procedural metrics were retrieved. Primary outcomes of interest include technical success and in-hospital mortality. Factors of mortality were assessed using a logistic regression model.ResultsTwenty-one patients were brought to the endovascular suite directly (endovascular group) from the trauma bay and 25 patients after treatment in the operating room (OR group). The OR group had higher hemodynamic instability (48.0% vs 19.0%, p = 0.040), lower hemoglobin (12.9 vs 10.1, p = 0.001) and platelet counts (235.2 vs 155.1, p = 0.003), and worse Acute Physiology and Chronic Health Evaluation (APACHE) score (4.1 vs 10.2, p < 0.0001) at the time of initial presentation. Technical success was achieved in all 40 cases in which targeted embolization was attempted (100%). Empiric embolization was performed in 6/46 (13.0%) patients based on computed tomographic angiogram (CTA) and operative findings. Stent-grafts were placed in 3 patients for subclavian artery injuries. Availability of pre-intervention CTA was associated with shorter fluoroscopy time (19.8 ± 12.1 vs 30.7 ± 18.6 min, p = 0.030). A total of 41 patients were discharged in stable condition (89.1%). Hollow organ injury was associated with mortality (p = 0.039).ConclusionEndovascular embolization and stenting were effective in managing hemorrhage due to GSW in a carefully selected population. Hollow organ injury was a statistically significant predictor of mortality. Pre-intervention CTA enabled targeted, shorter and equally effective procedures.

Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines.

Liver cancer is the third leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transarterial interventions are among the chemotherapeutic approaches used in hardly operable regions prior to transplantation, and in electrochemotherapy, where doxorubicin is used. However, the efficacy of treatment is affected by resistance mechanisms. Previously, we showed that overexpression of the CUE5 gene results in doxorubicin resistance in Saccharomyces cerevisiae (S. cerevisiae). In this study, the effect of Toll-interacting protein (TOLLIP), the human ortholog of CUE5, on doxorubicin resistance was evaluated in HCC cells to identify its possible role in increasing the efficacy of transarterial interventions. The NIH Gene Expression Omnibus (GEO) and Oncomine datasets were analyzed for HCC cell lines with relatively low and high TOLLIP expression, and SNU449 and Hep3B cell lines were chosen, respectively. TOLLIP expression was increased by plasmid transfection and decreased by TOLLIP-siRNA in both cell lines and evaluated by RT-PCR and ELISA. Cell proliferation and viability were examined using xCELLigence and MTT assays after doxorubicin treatment, and growth inhibitory 50 (GI 50) concentrations were evaluated. Doxorubicin GI 50 concentrations decreased approximately 2-folds in both cell lines upon silencing TOLLIP after 48h of drug treatment. Our results showed for the first time that silencing TOLLIP in hepatocellular carcinoma cells may help sensitize these cells to doxorubicin and increase the efficacy of chemotherapeutic regimens where doxorubicin is used.

Vein of Galen malformations in the newborn: case series.

Vein of Galen malformations (VoGMs) in newborns often represent life-threatening emergencies. Outcome is difficult to predict. The authors review 50 VoGM cases to correlate anatomical types with treatment and outcome. Four distinct types of VoGMs are identified: mural simple (type I), mural complex (type II), choroidal (type III), and choroidal with deep venous drainage (type IV). Seven patients presented with mural simple VoGMs with a "single hole" fistula supplied by only one large feeder. These patients were treated electively at >6 months; development was normal. Fifteen patients presented with complex mural VoGMs. Multiple large feeders joined a single fistulous point within the wall of the varix. Patients typically presented with congestive heart failure (CHF) and required emergent transarterial intervention. Mortality was 7.7% with less than two-thirds developing normally. Twenty-five patients presented with choroidal VoGMs. Multiple large arterial feeders joined at multiple fistulous sites. Severe CHF in most patients required emergent transarterial and sometimes transvenous intervention. Mortality was 9.5%; two-thirds of the patients had a normal development. Three babies presented with choroidal VoGMs with deep intraventricular venous drainage. This phenomenon caused fatal "melting brain syndrome" in all three patients. Recognition of the specific VoGM type determines treatment options and sets outcome expectations.

Lenvatinib in combination with PD-1 inhibitor and hepatic arterial infusion chemotherapy (HAIC) for patients with potentially resectable hepatocellular carcinoma: A retrospective analysis.

e16160 Background: Surgical resection is the primary radical treatment for hepatocellular carcinoma (HCC). However, the percentage of initially resectable HCC is only 15-30%, and most patients are unable to undergo surgical resection at the time of initial diagnosis. Lenvatinib combined with PD-1 inhibitor and transarterial intervention has demonstrated good efficacy and safety in unresectable HCC. The retrospective study was designed to explore the safety and conversion effects of lenvatinib + camrelizumab+ HAIC in potentially resectable HCC. Methods: In this single-arm retrospective study, investigators collected patients with potentially resectable HCC treated with lenvatinib + camrelizumab + HAIC from November 2020 to December 2022. The potentially resectable population was selected by the following screening criteria: acceptable liver function (Child-Pugh A-B), good ECOG PS (0-1), intrahepatic tumors confined to one lobe (left, right, or middle lobe), and unresectable by surgical or oncological causes. Results: A total of 64 patients with potentially resectable HCC were included in this analysis. The conversion rate was 31.25% (20), and 23.4% (15) patients underwent surgery. The ORR and DCR were 56.3% and 85.9% by RECIST 1.1. Progression had occurred in 8 patients by the data cutoff on November 1, 2022. The median follow-up time was 13.6 months (range: 2.9-23.7) and 8 patients died. The data was not yet mature, with 1-year survival rate of 90.7%, Overall, 65.6% of patients experienced at least one treatment emergent adverse event (TEAE) and 15.6% of patients had Grade 3/4 TEAE, the most common was hand and foot syndrome (7.8%, n=5). Conclusions: Lenvatinib combined with PD-1 inhibitor and HAIC was well tolerated and showed potential conversion efficacy in the treatment of patients with potentially resectable HCC.

Safety of sheathless vascular access using braided 4 F selective catheters for common body interventions – a retrospective study

BackgroundBesides other factors, complication rate of transarterial interventions depends on the size of the vascular access. Therefore, the vascular access is mostly chosen as small as possible while still allowing all planned parts of the intervention.This retrospective analysis is to evaluate the safety and feasibility of sheathless arterial interventions for a broad spectrum of interventions in daily practice.MethodsAll sheathless interventions using a 4 F main catheter between May 2018 and September 2021 were included in the evaluation. Additionally, intervention parameters such as type of catheter, use of microcatheter and required change of main catheters were assessed. Information about the use about sheathless approach and catheters were obtained from the material registration system. All catheters were braided.Results503 sheathless interventions with 4 F catheters from the groin were documented. The spectrum comprised bleeding embolization, diagnostic angiographies, arterial DOTA-TATE-therapy, uterine fibroid embolization, transarterial chemotherapy, transarterial radioembolization and others. In 31 cases (6 %) a change of the main catheter was required. In 381 cases (76 %) a microcatheter was utilized. No clinically relevant adverse events were observed (grade 2 or higher [CIRSE AE-classification]). None of the cases later required conversion to a sheath-based intervention.ConclusionsSheathless interventions with a 4 F braided catheter from the groin are safe and feasible. It allows for a broad spectrum of interventions in daily practice.

Role of Herbal Medicines in Hepatocellular Carcinoma

Mutation in several factors and pathways leads to the development of hepatic cancer i.e. Mutation in Wnt-β-Catenin Signalling Pathway , activation of the Insulin-Like Growth Factor (IGF) Signalling Pathway, The P13/PTEN/AKT, TP53 Tumour Suppressor Gene. Liver cirrhosis and fatty liver predispose the normal tissues to fibrosis leading to liver cancer. Excessive alcohol intake results in the inflammation of liver proceeding to cirrhosis and ultimately hepatic carcinoma. Hepatocellular Carcinoma (HCC) is multi-centric i.e. has huge variability in its spread which differs from person to person. Four approaches are practiced for treatment of hepatic cancer; surgery, transarterial intervention, percutaneous intervention, and drug approach. Surgery includes liver transplant and tumour resection. Transarterial approach includes chemoembolization and embolization. Percutaneous approach includes radiofrequency thermal ablation (RFTA) and ethanol injection. Drugs are various including herbal plant medicines, herbal formulae, synthetic drugs, immune, and gene therapies. Zingiber officinal, Schinus molle L., Zerumbone, Curcuma longa and Mammea siamensis are some of the plant medicines.

Comprehensive Review on Current Controversies and Debate in Prostate Artery Embolization.

Prostate artery embolization is emerging as one of the most effective therapies amidst a new era of mini- mally invasive benign prostate hyperplasia treatment and technology. However, several current controver- sies remain unanswered which could impact the widespread adoption of this novel and unique transarterial(rather than transurethral) intervention. This is reflected in the differences between the UK (NICE), European (EAU), and American (AUA) guidelines, the latter of which only recommends the use of prostate arteryembolization in a clinical trial setting. The main issues include questions over the duration of symptom response, cost-effectiveness, mechanism of action, patient selection, and other procedural technical consid- erations. These factors are the most pressing faced by proponents of prostate artery embolization, and we seek to highlight why their resolution is important to ensure men with benign prostate hyperplasia seeking a minimally invasive solution are optimally informed and most effectively managed.

Efficacy of Transarterial Intervention Combined with Ultrasound Radiofrequency Ablation for Liver Malignancy

Efficacy of Transarterial Intervention Combined with Ultrasound Radiofrequency Ablation for Liver Malignancy

Dual-energy CT with virtual monoenergetic images to improve the visualization of pancreatic supplying arteries: the normal anatomy and variations

BackgroundPancreatic ductal adenocarcinoma (PDAC) remains a malignancy with poor prognosis, appropriate surgical resection and neoadjuvant therapy depend on the accurate identification of pancreatic supplying arteries. We aim to evaluate the ability of monoenergetic images (MEI [+]) of dual-energy CT (DECT) to improve the visualization of pancreatic supplying arteries compared to conventional polyenergetic images (PEI) and investigate the implications of vascular variation in pancreatic surgery and transarterial interventions.ResultsOne hundred patients without pancreatic diseases underwent DECT examinations were retrospectively enrolled in this study. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) at 40-keV MEI (+) were significantly higher than those of PEI (p < 0.05). All subjective MEI (+) scores were significantly higher than those of PEI (p < 0.05). The visualization rates were significantly higher for posterior superior pancreaticoduodenal artery (PSPDA), anterior and posterior inferior pancreaticoduodenal artery (AIPDA, PIPDA), anterior and posterior pancreaticoduodenal arcade (APAC, PPAC), transverse and caudal pancreatic artery (TPA, PCA) at 40-keV MEI (+) than those of PEI (p < 0.05). However, there were no significant differences for visualizing anterior superior pancreaticoduodenal artery (ASPDA), inferior pancreaticoduodenal artery (IPDA), dorsal and magnificent pancreatic artery (DPA, MPA) between 40-keV MEI (+) and PEI (p > 0.05). Four types of variations were observed in the origin of DPA and three to five types in the origin of PSPDA, AIPDA and PIPDA.Conclusions40-keV MEI (+) of DECT improves the visualization and objective and subjective image quality of pancreatic supplying arteries compared to PEI. Pancreatic supplying arteries have great variations, which has important implications for preoperative planning of technically challenging surgeries and transarterial interventions.

Superior sagittal sinus dural arteriovenous fistula caused by treatment of meningioma masquerades as sinus thrombosis

Dural arteriovenous fistulas (DAVF) are rare acquired lesions resulting from abnormal shunting between intracranial dural arteries and venous system. Typically arising from structural weakness of the dura and a coinciding trigger factor, DAVFs can present with similar clinical and imaging characteristics to sinus thrombosis. A 61-year-old male with a history of meningioma previously managed with subtotal resection and stereotactic radiosurgery presented with progressive right-sided vision loss and bilateral papilledema. Initial imaging suggested possible sinus occlusion. Catheter angiogram revealed a Borden-Shucart grade III DAVF of the superior sagittal sinus and elevated venous pressures and the patient subsequently underwent endovascular transarterial intervention twice. We report on the first case of a superior sagittal sinus DAVF occurring after surgical resection of a parasagittal meningioma.

Safety, feasibility, and comfort of hepatic angiography and transarterial intervention with radial access for hepatocellular carcinoma.

Background and AimHepatic angiography procedures such as transarterial chemoembolization (TACE) are essential procedures for managing patients with hepatocellular carcinoma (HCC), and are usually performed with femoral access. However, femoral access causes patient discomfort and may be associated with the risk of hematoma or pseudoaneurysm at puncture site. We evaluated the safety, feasibility, and patient comfort of hepatic angiography procedures performed with radial access.MethodsIn this single‐institution, retrospective, time‐frame study, a total of 206 patients who underwent hepatic angiography procedures with radial access, which were first used on October 2017 at our institution, were compared with 240 patients who underwent the same procedures with femoral access before this period. Several measures were assessed, including procedure time and safety. In addition, a questionnaire was used to compare the access types regarding procedure‐associated discomfort.ResultsHepatic angiography procedures performed with radial access, including TACE, were completed in all patients without complications. The procedure time was comparable between radial access and femoral access. Most patients preferred radial to femoral access. Patients taking anticoagulants were able to complete the procedures without discontinuing these drugs.ConclusionsHepatic angiography procedures with radial access resulted in less discomfort than those with femoral access, and the two approaches showed similar feasibility and safety. Radial access can be introduced as a routine technique for hepatic angiography procedures.

A novel model of ischemia in rats with middle cerebral artery occlusion using a microcatheter and zirconia ball under fluoroscopy

The failure of neuroprotective treatment-related clinical trials may be partially caused by unestablished animal models. Existing animal models are less likely to provide occlusion confined to the middle cerebral artery (MCA), making transarterial intervention difficult. We aimed to develop a novel focal stroke model using a microcatheter and zirconium dioxide that is non-magnetic under fluoroscopic guidance, which can monitor MCA occlusion and can improve hemorrhagic complications. Using male Sprague Dawley rats (n = 10), a microcatheter was navigated from the caudal ventral artery to the left internal carotid artery using an X-ray fluoroscopy to establish local occlusion. All rat cerebral angiographies were successful. No rats had hemorrhagic complications. Eight (80%) rats underwent occlusion of the MCA bifurcation by zirconium dioxide. Accidentally, the left posterior cerebral artery was failure embolized in 2 rats (20%). The median operating time was 8 min. All rats of occlusion MCA revealed an incomplete hemiparesis on the right side with neurological deficit score ranging from 1 to 3 (median 1, interquartile range 1–3) at 24 h after the induction of ischemia. Moreover, 2% 2,3,5-triphenyl tetrazolium chloride staining showed that the median infarct volume (mm3) was 280 (interquartile range 267–333) 24 h after the left MCA bifurcation occlusion. We present a novel rat model for focal stroke using a microcatheter and zirconium dioxide which does not affect the MRI. The model is predictable which is well confined within the territory supplied by the MCA, and reproducibility of this model is 80%. Fluoroscopy was able to identify which the MCA occlusion and model success while creating the model. It permitted exclusion of animals with complications from the experiment.

Safety of ultrasound-guided distal radial artery access for abdominopelvic transarterial interventions: a prospective study

We aimed to evaluate ultrasound-guided distal radial artery (DRA) access to perform abdominopelvic endovascular procedures. A prospective, observational study was carried out in a single center between December 2017 and February 2019. Forty-two abdominopelvic endovascular procedures were performed by the same operator in 37 patients with DRA access using a 5 F sheath. Most patients were male (67.6%) with a mean age of 62.0±11.4 years (age range, 27.6-82.8 years). Patient characteristics, including Barbeau's test classification, radial and ulnar sizes and technical success, were evaluated. Patients with a DRA smaller than 1.7 mm could not be safely punctured and were not included. Procedures included chemoembolization of hepatocellular carcinoma in 35 cases (83.3%), embolization of hepatic metastasis in neuroendocrine tumors in 4 cases (9.5%) and other embolization procedures in 3 cases (7.1%). The mean diameters of the DRA, proximal radial artery and proximal ulnar artery were 2.31, 2.63, and 2.09 mm, respectively. Out of 42 DRA puncture attempts, 97.6% (41/42) were successfully performed. There were no postoperative complications related to the access site, such as pain, palsy, paresthesia, occlusion, finger ischemia, bleeding, hematoma, and pseudoaneurysm. Transient forearm discomfort was reported in 7.1% of patients (3/42); one occurrence was associated with kinking rectification, and two occurrences were attributed to small arteries and/or vasospasm. Ultrasound-guided DRA access seems to be feasible and safe to perform in abdominopelvic endovascular procedures in patients with a DRA considered amenable to be safely punctured, with high technical success rates.

Abstract 6136: Generation and characterization of colorectal cancer cell lines from the Buffalo rat

Abstract Introduction: Rat models of metastatic colorectal cancer (mCRC) to the liver are ideal for the development of transarterial therapies. To date, only one model of CRC cells grown in vitro and implanted into the liver of syngeneic rats is available. Yet, the small size of the WAG-Rij rat limits the use of the CC-531/WAG-Rij model for transarterial interventions. This work was aimed at generating an analogous model on the Buffalo rat, strain that has successfully been used for transarterial interventions in primary liver cancer. Materials and Methods: To induce CRC, 5 6-week old Buffalo rats were treated with Azoxymethane (AOM) and Dextran Sodium Sulfate (DSS). To assess tumor progression, the rats were regularly examined by colonoscopy as well as to T1- and T2-MR imaging from w20 up to w63. Standard procedures of tumor cell isolation and in vitro expansion were used. Once the polyclonal lines were established, expression of E-cadherin, Ceacam5, Mucin1, Vimentin1, and S100a4 was evaluated by flow cytometry (FACS) or qPCR. Additionally, the gene regions of APC (nt. 3049 to 3697) and β-catenin (nt. 371 to 1104) were analyzed by Sanger sequencing. Lastly, 23 adult Buffalo rats received implantations of 0.4-1 × 107 cells in the liver only or in the liver as well as subcutaneously. Results: Colonoscopies, MRIs, and histopathology demonstrated that all 5 rats treated with AOM/DSS developed colorectal neoplasms by w22. Tumors were harvested at various time points, at weeks 24, 32, 45, and 63. 2 polyclonal cell lines derived from invasive adenocarcinomas of a female (18L002) and a male (18L004) were successfully established and have proliferated in vitro &amp;gt;1year. FACS and qPCR results showed that both lines express the epithelial markers E-cadherin, Ceacam5, and Mucin1. Interestingly, despite high E-cadherin expression in both lines (&amp;gt;90% by FACS), qPCR data revealed that both lines also express the mesenchymal markers Vimentin and S100a4, suggestive of a trans-differentiated phenotype. DNA sequences of regions of the APC and β-catenin genes frequently mutated by AOM treatment appeared to be intact in both lines. MRIs of the 23 rats that received implants showed that 4 seem to have allowed for short-term growth (~14d) of the 18L004 cells in the liver before being re-absorbed. Histopathological analyses showed evidence of a serosal reaction at the site of implantation in those cases. Conclusions: Two polyclonal CRC lines with phenotypical characteristics of trans-differentiated cells were successfully generated from AOM/DSS-treated Buffalo rats. In spite of continued in vitro growth for over a year, neither line was tumorigenic in vivo, potentially due to the lack of mutations in key regions of the APC and β-catenin genes. Forced expression of mutant genes known to drive CRC progression such as β-catenin, Kras, or P53 could potentially increase in vivo tumorigenicity and allow for the establishment of a rat model of mCRC suitable for the study of transarterial therapies. Citation Format: Nina M. Muñoz, Crystal J. Dupuis, Katherine A. Dixon, Malea L. Williams, Kiersten L. Maldonado, Asif Rashid, Alda L. Tam. Generation and characterization of colorectal cancer cell lines from the Buffalo rat [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6136.

Risk Factors for In-hospital Mortality After Transarterial Intervention After Postpancreatectomy Hemorrhage

PurposePostpancreatectomy hemorrhage (PPH) is one of the leading causes of mortality after pancreatic resection. Late onset PPH is most often treated using a transarterial approach. The aim of this study was to analyze risk factors for in-hospital mortality after endovascular treatment.MethodsBetween 2012 and 2017, patients who were treated endovascular due to PPH were identified from a retrospective analysis of a database. Risk factors for mortality were identified by univariate analysis.ResultsIn total, 52 of the 622 patients (8.4%) underwent endovascular treatment due to PPH. The primary technical success achieved was 90.4%. In 59.6% of patients, bleeding control was achieved by placing a stent graft and in 40.4% by coil embolization. The primary 30-day and 1-year patency of the placed covered stents was 89.3% and 71.4%, respectively. The 60-day mortality was 34.6%. The reintervention rate was higher after stent graft placement compared to coiling (39.3% vs. 21.1%, P = 0.012). In the univariate analysis the need for reintervention was associated with a higher in-hospital mortality (21.2% vs. 7.7%, P = 0.049). The use of an antiplatelet agent was associated with a decreased in-hospital mortality in the univariate (11.5% vs. 25%, P = 0.024) and multivariate analysis (HR 3.1, 95% CI 1.1-9, P = 0.034), but did not increase the risk of rebleeding.ConclusionEndovascular management of delayed PPH has a high technical success rate. Stent graft placement showed a higher reintervention rate. The need for reintervention was associated with a higher in-hospital mortality but did not differ between coiling and stent graft placement.

How to Measure the Aorta Using MRI: A Practical Guide.

How to Measure the Aorta Using MRI: A Practical Guide.

Yttrium-90 microsphere radioembolisation for unresectable hepatocellular carcinoma.

Due to a comment received and due to some other identified methodological problems, the present review is withdrawn.

Hepatocellular carcinoma: An Update

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not significantly improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and the limited therapeutic options. The therapeutic options fall into several categories: (i) surgical interventions including tumor resection and liver transplantation, (ii) percutaneous interventions including ethanol injection and radiofrequency thermal ablation, (iii) transarterial interventions including embolization, chemoembolization and selective internal radiotherapy, (iv) external radiation therapy and (v) systemic strategies with cytotoxic agents and molecularly targeted therapies as well as immunotherapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for actual therapeutic recommendations. While surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, &lt;5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% of patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care (BSC). In order to reduce the morbidity and mortality from HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including cytotoxic agents, molecular targeted and immunotherapies is most important. New analytical technologies, including gene expression profiling and proteomic analyses and others, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.